Stable liquid formulations for pharmaceuticals and supplements

ABSTRACT

A liquid composition comprising: a primary component being an Active Pharmaceutical Ingredient (API), a nutritional supplement, or combinations thereof: a base; and a preservative blend is provided along with a method of making said composition.

INDEX TO RELATED APPLICATIONS

This application is a continuation of U.S. Non-provisional patentapplication Ser. No. 15/912,785 Filed Mar. 6, 2018 which is anon-provisional of, and claims benefit to U.S. Provisional PatentApplication Ser. No. 62/580,648 filed Nov. 2, 2017 the disclosures ofwhich are incorporated herein by reference in their entirety.

SUMMARY OF THE INVENTION

The present invention relates to novel stabilization of liquidpharmaceutical and nutritional supplements.

In one embodiment, the present invention is a liquid compositioncomprising:

-   -   a primary component being an Active Pharmaceutical Ingredient        (API), a nutritional supplement, or combinations thereof:    -   a base;    -   a preservative blend comprising either, Organic Cultured        Dextrose, Organic Elderberry (16:1 Fruit Powder)

Organic Compliant Citric Acid

Organic Turmeric Root Powder

Organic Fennel Seed Powder

Organic Ginger Root, in a ratio of1:0.8-1.0:0.55-0.65:0.40-0.54:0.05-0.09:0.05-0.09 or

Organic Cultured Dextrose

Organic Elderberry (16:1 Fruit Powder)

Organic Compliant Citric Acid

Organic Echinacea Purpurea Herb (6:1), in a ratio of1:0.60-0.70:0.55-0.65:0.35-0.44.

In one embodiment, the present invention provides the preservative blendis 2-5% w/w of the composition.

In one embodiment, the present invention is a liquid compositionconsisting of:

-   -   a primary component being an Active Pharmaceutical Ingredient        (API), a nutritional supplement, or combinations thereof:    -   a base;    -   a preservative blend comprising either, Organic Cultured        Dextrose, Organic Elderberry (16:1 Fruit Powder)

Organic Compliant Citric Acid

Organic Turmeric Root Powder

Organic Fennel Seed Powder

Organic Ginger Root, in a ratio of1:0.8-1.0:0.55-0.65:0.40-0.54:0.05-0.09:0.05-0.09 or

Organic Cultured Dextrose

Organic Elderberry (16:1 Fruit Powder)

Organic Compliant Citric Acid

Organic Echinacea Purpurea Herb (6:1), in a ratio of1:0.60-0.70:0.55-0.65:0.35-0.44.

In one embodiment, the present invention is a method of preparing aliquid composition as described herein comprising the steps of:

Providing components of a preservative blend comprising either OrganicCompliant Citric Acid

Organic Turmeric Root Powder

Organic Fennel Seed Powder

Organic Ginger Root, or

Organic Cultured Dextrose

Organic Elderberry (16:1 Fruit Powder)

Organic Compliant Citric Acid

Organic Echinacea Purpurea Herb (6:1),

-   -   and combing them into an herbal pre-mix, blend into a small        amount of the base and heat between 180-200 degrees Fahrenheit,        to create the pre-mix containing the herbal ingredients;

combining the pre-mix and mix with the remainder of the agave/honey (themajority of the formula), which was heated to about 100° F. degreesuntil the pre-mix is homogenous and becomes one product;

cooling the combined mixture to room temperature and introduce flavorsonce at room temperature;

placing the combined cooled room temperature product containing flavors(pre-mix and remainder of formula); and

mixing to form a uniform composition.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

The present invention relates to novel stabilization of liquidpharmaceutical and nutritional supplements.

Although the examples provided herein are nutritional supplements, it iscontemplated that any Active Pharmaceutical Ingredient (API) ornutritional supplement ingredient is formulated according to theinvention disclosed herein and will produce a stable composition withdesired shelf life.

In one embodiment, the present invention includes the process ofblending an herbal pre-mix with a small amount of the base (in thiscase, agave or honey) and heating at a high temperature (about 180-200degrees Fahrenheit), subsequently mixing the pre-mix with the remainderof the formula, which has been heated to be at a lower temperature(about 100° F.). By heating the pre-mix and base and the remainder ofbase separately and at different temperatures, the novel process willreduce the froth and prevent flavor changes. This is the first time sucha system has been used.

In one embodiment, the present invention includes using approximately80-90% solid base (in this case, 84% solid agave or honey depending)with combination of cultured dextrose and citric acid in order to nothave to put in a non-organic, synthetic preservative systems. Thisallows the present invention to have a certified organic base withoutany synthetic preservative systems. This is the first time thiscombination of high percentage solid base, citric acid and cultureddextrose has been used.

In formulations practice, it is known that often two or morepreservatives are provided. Sometimes they are provided for specificpreserving characteristics. However, there are preservative systems thatare utilized with various components having beneficial synergisticaffects even thought the exact mechanism of the beneficial synergisticaffects is not clearly understood. This is true in the presentformulation whereby a synergistic system has been discovered,demonstrated effective, yet is operating in a mechanism not fullyunderstood.

In the present invention, particular ratios have been discovered wherebya plurality of components in the ratios herein, provide the desiredeffect.

Initial formulas were exactly the same, except the agave was around60-70% solid and they did not have cultured dextrose. These formulas didnot have an effective preservation system, and failed stability testing.

Manufacture

In one embodiment, the present invention is performed using thefollowing steps:

Providing organic herbal extracts and combing them into an herbalpre-mix, blend into a small amount of the base (here, agave or honeydepending) and heat between 180-200 degrees Fahrenheit, to create thepre-mix containing the herbal ingredients.

Although the examples demonstrate Agave and Honey as the base, the term“base” as used herein includes components having similar viscosities andcharacteristics including, but not limited to tapioca syrups, fruitsyrups, maple syrups, elderberry syrup, combinations of bases, and thelike.

As is known, Agave will break down at 320° F. and will even begin tochange at 210° F., therefore 180-200° F. is one ideal temperature rangeto extract the herbal ingredients into the agave/honey without hurtingthem or the agave/honey. The present invention contemplates temperaturefor other types of syrups with similar consistencies at similartemperatures.

Combining the pre-mix and mix with the remainder of the agave/honey (themajority of the formula), which was heated to about 100° F. degreesuntil the pre-mix is homogenous and becomes one product.

Cooling the combined mixture to room temperature and introduce flavorsonce at room temperature.

Placing the combined cooled room temperature product containing flavors(pre-mix and remainder of formula) and mix into a mixer.

It has been discovered that separately handling the pre-mix andremainder of formula separately, prevents flavor changes and froth. Thisthen helps reduce and prevent sheer and flavor changes as the sheer andflavor changes are caused by warming at a high temperature. Heating theherbal pre-mix is necessary to blend the herbal ingredients into thebase.

Sample Formulations

FORMULA 1 AGAVE COUGH SYRUP Organic Agave Syrup 4.6 g Organic Acerola 29mg (containing 34% naturally occurring Vitamin C) Proprietary Blend: 27mg Organic Elderberry Fruit Powder (16:1), Organic Fennel Extract,Organic Turmeric, Organic Ginger Root.

FORMULA 2 HONEY COUGH SYRUP Organic Honey 6.3 g Organic Echinacea 15 mgOrganic Elderberry Fruit Powder (16:1) 25 mg Organic Acerola 75 mg(containing 34% naturally occurring Vitamin C)

FORMULA 3 AGAVE TEETHING SYRUP Organic Agave Syrup 4.6 g Organic Acerola29 mg (containing 34% naturally occurring Vitamin C) Proprietary Blend:25 mg Organic Elderberry Fruit Powder (16:1), Organic Turmeric, OrganicReishi Mushroom.

Agave Cough Syrup Percentage Composition Mg per Formulation servingPercentage Organic Agave Syrup 2894.28  96.4761172% Organic Acerola (34%Vitamin C) 30.88   1.0254118% Organic Cultured Dextrose 24.26  0.8085000% Organic Elderberry (16:1 Fruit Powder) 21.00   0.7000000%Organic Compliant Citric Add 14.45   0.4816700% Organic Cherry Flavor11.13   0.3709677% Organic Reishi Mushroom Powder 2.00   0.0666667%Organic Turmeric Root Powder 2.00   0.0666667% Total: 3,000.00100.000000%

Honey Cough Syrup Percentage Composition Mg per Formulation: servingPercentage Organic Honey 4,530.88  90.6176871% Purified Water 285.71  5.7142857% Organic Acerola (34% Vitamin C) 78.75   1.5750000% OrganicCultured Dextrose 40.43   0.8085000% Organic Elderberry (16.1 Fruit25.00   0.5000000% Powder) Organic Compliant Citric Acid 24.08  0.4816700% Organic Echinacea Purpurea Herb 15.00   0.3000000% (6:1)Organic Compliant Lemon Flavor 0.14   0.0028571% Total: 5,000.00100.000000%

Agave Teething Syrup Mg per Formulation: serving: Percentage OrganicAgave Syrup 2,892.18  96.4094505% Organic Acerola (34% Vitamin C) 30.88  1.0294118% Organic Cultured Dextrose 24.26   0.8085000% OrganicElderberry (16:1 Fruit Powder) 21.00   0.7000000% Organic CompliantCitric Acid 14.45   0.4816700% Organic Cherry Flavor 11.13   0.3709677%Organic Turmeric Root Powder 2.00   0.0666667% Organic Fennel SeedPowder 2.00   0.0666667% Organic Ginger Root 2.00   0.0666667% Total:3,000.00 100.000000%

Preservative Efficay Testing USP Preservative Efficay

Agave Cough Syrup Inoculum ATCC Test Organisms Level (CFU/g) NumberEscherichia coli 4.9 × 10⁵ 8739 Pseudomonas aeruginosa 6.0 × 10⁵ 9027Staphylococcus aureus 5.0 × 10⁵ 6538 Candida albicans 2.6 × 10⁵ 10231Aspergillus (niger) 3.1 × 10⁵ 16404 brasiliensis

Method

The sample was challenged against the five individual microorganismslisted above following the USP <51> guidelines. Pure culture challengeyields specific data on each microorganism employed in the study.

The sample was initially tested for aerobic bacteria, yeast, and moldfollowing the USP <51> guidelines. This initial screen is imperative toensure the product does not contain any microorganisms prior tobeginning the inoculations. No organisms were found in the sample duringthe initial screen.

Effectiveness Standards

Bacteria: Not less than 1.0 log reduction from the initial count at 14days, and no increase from the 14 days' count at 28 days. Yeast andMolds: No increase from the initial calculated count at 14 and 28 days.Upon reinoculation, the same effectiveness standards apply.

Test E. P. S. C. A. Interval coli aeruginosa aureus Albicansbrasiliensis 0 hours 1.8 × 10⁵ 2.8 × 10⁴ 6.7 × 10⁵ 2.0 × 10³ 2.2 × 10⁴ 1Week  210 260 190 <10 2.2 × 10³ 2 Weeks <10 <10 <10 <10   30 4 Weeks <10<10 <10 <10 <10 All results in the table are reported as CFU/g

Study Conclusion The sample has PASSED the test. The actual datacollected from the study at each testing interval is listed on thefollowing page.

USP Preservative Efficay

Honey Cough Syrup Inoculum ATCC Test Organism Level (CFU/g) NumberEscherichia coli 4.9 × 10⁵ 8739 Pseudomonas aeruginosa 6.0 × 10⁵ 9027Staphylococcus aureus 5.0 × 10⁵ 6538 Candida albicans 2.6 × 10⁵ 10231Aspergillus (niger) 3.1 × 10⁵ 16404 brasiliensis

Method

The sample was challenged against the five individual microorganismslisted above following the USP <51> guidelines. Pure culture challengeyields specific data on each microorganism employed in the study.

The sample was initially tested for aerobic bacteria, yeast, and moldfollowing the USP <51> guidelines. This initial screen is imperative toensure the product does not contain any microorganisms prior tobeginning the inoculations. No organisms were found in the sample duringthe initial screen.

Effectiveness Standards

Bacteria: Not less than 1.0 log reduction from the initial count at 14days, and no increase from the 14 days' count at 28 days. Yeast andMolds: No increase from the initial calculated count at 14 and 28 days.Upon reinoculation, the same effectiveness standards apply.

Test E. P. S. C. A. Interval coli aeruginosa aureus albicansbrasiliensis 0 hours 5.1 × 10⁵ 1.3 × 10⁵ 9.7 × 10⁵ 1.2 × 10⁵ 2.4 × 10⁴ 1Week  120 86 5.2 × 10⁴ 10 1.9 × 10⁴ 2 Weeks <10 <10 <10 <10 2.1 × 10³ 4Weeks <10 <10 <10 <10 850 All results in the table are reported as CFU/g

Study Conclusion The sample has PASSED the test. The actual datacollected from the study at each testing interval is listed on thefollowing page.

USP Preservative Efficay

Agave Teething Syrup Inoculum ATCC Test Organism Level (CFU/g) NumberEscherichia coli 4.9 × 10⁵ 8739 Pseudomonas aeruginosa 6.0 × 10⁵ 9027Staphylococcus aureus 5.0 × 10⁵ 6538 Candida albicans 2.6 × 10⁵ 10231Aspergillus (niger) 3.1 × 10⁵ 16404 brasiliensis

Method

The sample was challenged against the five individual microorganismslisted above following the USP <51> guidelines. Pure culture challengeyields specific data on each microorganism employed in the study.

The sample was initially tested for aerobic bacteria, yeast, and moldfollowing the USP <51> guidelines. This initial screen is imperative toensure the product does not contain any microorganisms prior tobeginning the inoculations. No organisms were found in the sample duringthe initial screen.

Effectiveness Standards

Bacteria: Not less than 1.0 log reduction from the initial count at 14days, and no increase from the 14 days' count at 28 days. Yeast andMolds: No increase from the initial calculated count at 14 and 28 days.Upon reinoculation, the same effectiveness standards apply.

Test E. P. S. C. A. Interval coli aeruginosa aureus albicansbrasiliensis 0 hours 1.7 × 10⁵ 2.4 × 10⁴ 5.6 × 10⁵ 1.2 × 10³  2.5 × 10⁴1 Week  300 190 190 <10  805 × 10³ 2 Weeks <10 <10 <10 <10 40 4 Weeks<10 <10 <10 <10 <10 All results in the table are reported as CFU/g

Study Conclusion The sample has PASSED the test. The actual datacollected from the study at each testing interval is listed on thefollowing page.

The following represents the blend of ingredients demonstrative of oneembodiment of the novel preservative system:

Preservative Blend 1

Organic Cultured Dextrose

Organic Elderberry (16:1 Fruit Powder)

Organic Compliant Citric Acid

Organic Turmeric Root Powder

Organic Fennel Seed Powder

Organic Ginger Root

In one embodiment, these are combined in a ratio of1:0.8-1.0:0.55-0.65:0.40-0.54:0.05-0.09:0.05-0.09.

Preservative Blend 2

Organic Cultured Dextrose

Organic Elderberry (16:1 Fruit Powder)

Organic Compliant Citric Acid

Organic Echinacea Purpurea Herb (6:1)

In one embodiment, these are combined in a ratio of1:0.60-0.70:0.55-0.65:0.35-0.44.

The blend is used at 2-5% w/w of the final formulation. As evidenced bythe USP testing disclosed herein, formulations utilizing this stabilitysystem have demonstrated stability.

While the invention has been described in its preferred form orembodiment with some degree of particularity, it is understood that thisdescription has been given only by way of example and that numerouschanges in the details of construction, fabrication, and use, includingthe combination and arrangement of parts, may be made without departingfrom the spirit and scope of the invention.

What is claimed:
 1. A liquid composition comprising: a primary componentbeing an Active Pharmaceutical Ingredient (API), a nutritionalsupplement, or combinations thereof: a base; a preservative blendcomprising either, Organic Cultured Dextrose, Organic Elderberry (16:1Fruit Powder) Organic Compliant Citric Acid Organic Turmeric Root PowderOrganic Fennel Seed Powder Organic Ginger Root, in a ratio of1:0.8-1.0:0.55-0.65:0.40-0.54:0.05-0.09:0.05-0.09 or Organic CulturedDextrose Organic Elderberry (16:1 Fruit Powder) Organic Compliant CitricAcid Organic Echinacea Purpurea Herb (6:1), in a ratio of1:0.60-0.70:0.55-0.65:0.35-0.44.
 2. The composition of claim 1 whereinthe preservative blend is 2-5% w/w of the composition.
 3. A method ofpreparing a liquid composition comprising the steps of: Providingcomponents of a preservative blend comprising either Organic CompliantCitric Acid Organic Turmeric Root Powder Organic Fennel Seed PowderOrganic Ginger Root, or Organic Cultured Dextrose Organic Elderberry(16:1 Fruit Powder) Organic Compliant Citric Acid Organic EchinaceaPurpurea Herb (6:1), and combing them into an herbal pre-mix, blend intoa small amount of the base and heat between 180-200 degrees Fahrenheit,to create the pre-mix containing the herbal ingredients; combining thepre-mix and mix with the remainder of the agave/honey (the majority ofthe formula), which was heated to about 100° F. degrees until thepre-mix is homogenous and becomes one product; cooling the combinedmixture to room temperature and introduce flavors once at roomtemperature; placing the combined cooled room temperature productcontaining flavors (pre-mix and remainder of formula); and mixing toform a uniform composition.